Triethylamine → 2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-6-iodo-8-methyl-4H-3,1-benzoxazin-4-one

HRID 1296531Notes

Reaction equation

HRID 1296531 reaction equation
CS(Cl)(=O)=O.[Cl:6][C:7]1[C:8]([N:13]2[C:17]([C:18]([OH:20])=O)=[CH:16][C:15]([C:21]([F:24])([F:23])[F:22])=[N:14]2)=[N:9][CH:10]=[CH:11][CH:12]=1.C(N(CC)CC)C.[NH2:32][C:33]1[C:41]([CH3:42])=[CH:40][C:39]([I:43])=[CH:38][C:34]=1[C:35](O)=[O:36]>C(#N)C>[Cl:6][C:7]1[C:8]([N:13]2[C:17]([C:18]3[O:20][C:35](=[O:36])[C:34]4[CH:38]=[C:39]([I:43])[CH:40]=[C:41]([CH3:42])[C:33]=4[N:32]=3)=[CH:16][C:15]([C:21]([F:24])([F:23])[F:22])=[N:14]2)=[N:9][CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 112312332-Amino-5-iodo-3-methylbenzoic AcidHCID 113921841-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid2×

Product 1

HCID 184469312-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-6-iodo-8-methyl-4H-3,1-benzoxazin-4-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of methanesulfonyl chloride (2.91 mL, 37.74 mmol) in acetonitrile (50 mL) was added dropwise a mixture of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (i.e. the carboxylic acid product of Step C) (10.0 g, 34.31 mmol) and triethylamine (4.78 mL, 34.31 mmol) in acetonitrile (50 mL) at −5° C. The reaction temperature was then maintained at 0° C. throughout successive addition of reagents. After stirring for 20 minutes, 2-amino-3-methyl-5-iodobenzoic acid (i.e. the product from Step A) (9.51 g, 34.31 mmol) was added and stirring was continued for an additional 10 minutes. A solution of triethylamine (9.56 mL, 68.62 mmol) in acetonitrile (15 mL) was then added dropwise, and the reaction mixture was stirred 30 minutes, followed by the addition of methanesulfonyl chloride (2.91 mL, 37.74 mmol). The reaction mixture was then warmed to room temperature and stirred 2 hours. The solvent was evaporated under reduced pressure, and the residual solid was purified by chromatography on silica gel to afford 8.53 g of the title compound as a yellow solid.

Workup

  1. stirringstirring
  2. waitwas continued for an additional 10 minutes
  3. stirringthe reaction mixture was stirred 30 minutes
  4. temperatureThe reaction mixture was then warmed to room temperature
  5. stirringstirred 2 hours
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residual solid was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-bd89eeaaf34b4c42a96fadc232d6ec04
Source dataset
uspto-grants-2007_07
Patent number
US07247647B2

Reaction notes

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